Seperack P K, Mercer J A, Strobel M C, Copeland N G, Jenkins N A
Institute for Arthritis and Autoimmunity, West Haven, CT 06516, USA.
EMBO J. 1995 May 15;14(10):2326-32. doi: 10.1002/j.1460-2075.1995.tb07227.x.
The murine dilute coat color locus encodes an unconventional myosin heavy chain that is thought to be required for the elaboration or maintenance of dendrites or organelle transport in melanocytes and neurons. In previous studies we showed that the d mutation carried by many inbred strains of mice (now referred to as dilute viral, dv), is caused by the integration of an ecotropic murine leukemia virus (Emv-3) into the dilute gene and that phenotypic revertants of dv (termed d+) result from viral excision; a solo viral long terminal repeat (LTR) is all that remains in revertant DNA. In the studies described here we show that Emv-3 sequences are located within an intron of the dilute gene in a region of the C-terminal tail that is differentially spliced. We also show that these Emv-3 sequences result in the production of shortened and abnormally spliced dilute transcripts and that the level of this effect varies among tissues. This tissue-specific effect on dilute expression likely accounts for the absence of neurological abnormalities observed in dv mice. Surprisingly, we also found that the solo viral LTR present in revertant d+ DNA produces a tissue-specific effect on dilute expression, although this effect is less dramatic than with the full-length provirus and produces no obvious mutant phenotype. These findings have important implications for understanding the effects of viral sequences on mammalian gene expression.
小鼠淡化毛色基因座编码一种非常规肌球蛋白重链，它被认为是黑素细胞和神经元中树突的形成或维持以及细胞器运输所必需的。在先前的研究中，我们表明许多近交系小鼠携带的d突变（现在称为稀释病毒，dv）是由嗜亲性小鼠白血病病毒（Emv-3）整合到稀释基因中引起的，并且dv的表型回复体（称为d+）是由病毒切除产生的；回复体DNA中仅剩下一个单独的病毒长末端重复序列（LTR）。在本文所述的研究中，我们表明Emv-3序列位于稀释基因的一个内含子内，该内含子位于C末端尾巴的一个区域，该区域存在差异剪接。我们还表明，这些Emv-3序列导致产生缩短且异常剪接的稀释转录本，并且这种效应的水平在不同组织中有所不同。这种对稀释表达的组织特异性效应可能解释了在dv小鼠中未观察到神经学异常的原因。令人惊讶的是，我们还发现回复体d+ DNA中存在的单独病毒LTR对稀释表达产生组织特异性效应，尽管这种效应不如全长前病毒明显，并且不会产生明显的突变表型。这些发现对于理解病毒序列对哺乳动物基因表达的影响具有重要意义。
